Substance P, an 11-amino-acid neuropeptide, promotes fibrosis (scarring) in the liver, lungs, heart, kidneys, and gut through its NK-1 receptor, and blocking this receptor may slow or prevent fibrotic disease progression.
7+ organ systemsNumber of organ systems where Substance P/NK-1R signaling has been implicated in fibrotic disease processes
What the researchers found
The Substance P/NK-1 receptor (SP/NK-1R) system is implicated in fibrotic processes across multiple organ systems, including wound healing, myocardial fibrosis, bowel fibrosis, myelofibrosis, renal fibrosis, lung fibrosis, and liver fibrosis.
Recent studies have specifically demonstrated that Substance P plays an important role in liver fibrosis and that NK-1R antagonists can inhibit the progression of this fibrosis. The review proposes that NK-1R receptor antagonists could provide clinical solutions for treating fibrotic diseases more broadly.
Why it matters
Fibrotic diseases — where excessive scarring damages organs — affect millions of people and have limited treatment options. Identifying Substance P as a common driver across multiple types of fibrosis opens up a potentially unifying therapeutic strategy. Since NK-1R antagonists already exist (aprepitant is FDA-approved for nausea), there's a realistic path to repurposing these drugs for fibrotic conditions, which could accelerate clinical translation.
How the study worked
This is a narrative review article summarizing the existing literature on Substance P's structure, function, distribution, and involvement in fibrotic diseases across multiple organ systems. It synthesizes findings from preclinical and clinical studies.
What this study cannot tell us
As a narrative review, this paper summarizes existing literature without performing a systematic search or meta-analysis, which may introduce selection bias. Most evidence for NK-1R antagonists inhibiting fibrosis comes from preclinical (animal or cell) studies. Clinical trials specifically testing NK-1R antagonists for fibrotic diseases in humans are largely absent from this review. The mechanisms described are still partially speculative.
How to read the evidence
This is a narrative review synthesizing existing research. It provides a useful overview of the SP/NK-1R system's role in fibrosis but does not present new primary data. Most supporting evidence comes from preclinical studies rather than clinical trials.
When this study was published
Published in 2019, this review captures knowledge up to that point. The field of anti-fibrotic peptide therapeutics has continued to evolve, but the core mechanistic insights about Substance P's role remain relevant.
The bigger picture
This review connects neuropeptide biology to fibrotic disease, an area where treatment options remain limited. The finding that a single peptide signaling system (SP/NK-1R) contributes to scarring across so many different organs suggests a shared mechanism that could be therapeutically targeted. It also highlights the broader trend of neuropeptides being recognized as important players in diseases beyond the nervous system, including inflammation and tissue remodeling.
Questions still open
- Can existing NK-1R antagonists like aprepitant be repurposed at effective doses for treating organ fibrosis in humans?
- Does blocking Substance P signaling affect beneficial aspects of wound healing while suppressing pathological fibrosis?
- Are certain organ-specific fibroses more responsive to NK-1R blockade than others?
Common questions
What is Substance P and what does it normally do in the body?
Could existing anti-nausea drugs help treat fibrosis?
Read the original research
Substance P and fibrotic diseases.
Neuropeptides, 76, 101941
Citation
Peng, Lei; Agogo, George O; Guo, Jianqiang; Yan, Ming. (2019). Substance P and fibrotic diseases.. Neuropeptides, 76, 101941. https://doi.org/10.1016/j.npep.2019.101941